Chapter 8 - Exploring the role of protein quality control in aging and age-associated neurodegenerative diseases

Abstract

One of the hallmarks of aging and age-related neurodegenerative diseases (NDs) is neuronal cell death. The postmitotic nature of neurons further exacerbates the disease conditions as neuronal cell loss results in irreversible damage to the nervous system tissues. One of the mechanisms underlying aging and age-related NDs includes excessive aggregation of misfolded proteins within the cells. Cells possess biological processes, such as the protein quality control (PQC) system which facilitates efficient clearance of these proteins and protects the cells from their detrimental consequences. This keeps the cellular proteome intact and helps maintain a healthy state of cell that contributes directly toward the lifespan of any organism. However, the capacity of PQC system to manage cellular proteome declines with age and in age-related NDs, which leads to aggregation of misfolded proteins. This potentially expedites the process of cellular aging and onset or progression of age-associated NDs, as aggregation of misfolded proteins alters cellular functions and eventually results in cell death. There is no cure available for aging and age-associated NDs. The currently available therapeutics for NDs only provide limited improvements and are primarily for patients exhibiting disease symptoms. Thus there is a need for development of effective therapeutics which can decelerate aging and prevent or delay the onset or progression of these diseases. Manipulating the levels of components of the PQC system has gained lot of attention and raised a possibility of this system to serve as a therapeutic target. This chapter provides insights on the importance of the PQC system in working toward clearing of misfolded proteins in a precise fashion. This chapter also discusses its modulatory effect on protein misfolding and identifies therapeutic strategies that have been utilized or could potentially be used to boost the functioning of PQC system in aging and as a treatment for age-related NDs.